Biofilms, which are also called biological films or slime, refer in general to the structures formed byintracellularly producing polymeric materials such as polysaccharides, proteins and the like by microorganisms that attach themselves on the surface of a material and proliferate in an aqueoussystem. When biofilms are formed, there occurs hazard caused by microorganisms, and various industrial problems are raised. For instance, when biofilms are formed inside the pipeline of a food processing plant, these biofilms are peeled off, leading to incorporation of foreign substances into food products, as well as causing food borne disease due to the toxins derived from microorganisms. Furthermore, formation of biofilms on metal surfaces is causative of metal corrosion, thereby accelerating decrepitude of facilities.
In addition, with regard to the microbial aggregates which have already formed a biofilm, no sufficient effects are exhibited by microbial control agents such as bactericides or bacteriostatic agents in many cases, as compared with the case with regard to microorganisms which are in the state of being dispersed and floating in an aqueous system. For example, in the aspect of the medical field, there have been many reports in recent years on the cases of in-hospital infection caused by the biofilms formed by microorganisms that survive in narrow interstices or pores of medical instruments. It is well known that the biofilms formed on the teeth in human oral cavity, so-called dental plaques (tooth plaques), are causative of dental caries or gum diseases, and thus, investigation has been conducted on these problems for a long time.
Heretofore, the idea of inhibiting microbial growth by exerting a bactericidal action or bacteriostatic action on microorganisms, particularly bacteria, in order to inhibit biofilms, has been generally examined. Patent Document 1 or Patent Document 2 discloses that the number of bacterial cells is reduced by using fatty acids or aliphatic alcohols, and consequently the adhesion of bacteria onto an object material can be prevented. In particular, Patent Document 1 shows that a composition prepared from an antimicrobial oil phase and emulsifiers as an emulsion exhibits an effect of reducing the number of bacterial cells in a relatively short time, and thus discloses the idea of inhibiting adhesion of bacteria on the surface of the object material on the basis of the phenomenon that the absolute number of bacterial cells per unit volume is decreased. Furthermore, Patent Document 3 discloses a toothpaste composition and the like in which non-aqueous active ingredients such as anti-inflammatory drugs and the like are dissolved in an oily material, while Patent Document 4 discloses a method of preventing establishment of contaminative organisms (barnacles, bacterial slimes or the like) on underwater structures by contacting the contaminative organisms with specific alkylamine derivatives, but neither was effective in inhibiting the formation of biofilms. Furthermore, Patent Document 5 describes a method of inhibiting bacterial adhesion on the surfaces that are immersed in the water, using polyglycol fatty acid esters, and discloses that bacterial adhesion is effectively inhibited at a concentration far lower than the threshold level exhibiting biocidal activity of polyglycol fatty acid esters. Patent Document 6 also discloses an industrial preservative and antifungal agent containing a polyglycerine monofatty acid ester and the like.
Patent Document 1 or 2 describes an evaluation of bactericidal property (reducing the number of bacterial cells by about 4 orders of magnitude) in the case of contacting microorganisms with a bactericidal or antimicrobial composition for a relatively short time of 60 minutes or less. However, since the problem of biofilm takes place over a long time in the order of days to months, it is in fact difficult to draw a conclusion from such short-term evaluation of bactericidal property, on the control of inhibition of biofilm formation. The fatty acids or aliphatic alcohols mentioned as an antibacterial oil phase cannot be said to have a sufficient bactericidal effect on all microorganisms (bacteria), and particularly with regard to gram-negative bacteria which frequently cause problems by forming biofilms, the substances do not have the minimal inhibitory concentration (MIC), which is an index of the bactericidal effect on a long-term basis (Jon J. Kabara ed., Cosmetic and Drug Preservation; Principles and Practice, Fragrance Journal, Ltd., 1990). Moreover, according to an experiment performed by the present inventors, the composition described in Patent Document 1 or Patent Document 2 exhibits, as described therein, a short-term (up to about 3 hours) bactericidal effect on gram-negative bacteria, particularly on Pseudomonas or Serratia, but there was no indication of bactericidal property, or even of bacteriostatic effects of inhibiting microbial growth, on a long-term basis (1 day or longer), and eventually formation of biofilms was confirmed.
In addition to these, there are bactericidal drugs with a high bactericidal property, having the feature of showing an immediate effect, such as cationic surfactants, hypochlorite and the like having a high bactericidal property. However, since their bactericidal property rapidly disappears in the presence of organic substances in the system, it is difficult to maintain the effect of reducing the number of microbes over a long time as described above.
For these reasons, it was difficult to fundamentally inhibit the formation of biofilms from the viewpoint of bactericide or bacteriostasis of bacteria.    Patent Citation 1: JP-A-2002-524257 (WO 00/15562)    Patent Citation 2: JP-A-2004-513153 (WO 02/038181)    Patent Citation 3: JP-A-2005-289917    Patent Citation 4: JP-A-2004-525935 (WO 02/076928)    Patent Citation 5: JP-A-(Hei) 11-512720 (WO 97/11912)    Patent Citation 6: JP-A-2003-160410